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Respiratory Research
Published in: Respiratory Research 1/2020

Open Access 01-12-2020 | Idiopathic Pulmonary Fibrosis | Research

TRIM72 promotes alveolar epithelial cell membrane repair and ameliorates lung fibrosis

Authors: Xiaofei Cong, Nagaraja Nagre, Jeremy Herrera, Andrew C. Pearson, Ian Pepper, Robell Morehouse, Hong-Long Ji, Dianhua Jiang, Rolf D. Hubmayr, Xiaoli Zhao

Published in: Respiratory Research | Issue 1/2020

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Abstract

Background

Chronic tissue injury was shown to induce progressive scarring in fibrotic diseases such as idiopathic pulmonary fibrosis (IPF), while an array of repair/regeneration and stress responses come to equilibrium to determine the outcome of injury at the organ level. In the lung, type I alveolar epithelial (ATI) cells constitute the epithelial barrier, while type II alveolar epithelial (ATII) cells play a pivotal role in regenerating the injured distal lungs. It had been demonstrated that eukaryotic cells possess repair machinery that can quickly patch the damaged plasma membrane after injury, and our previous studies discovered the membrane-mending role of Tripartite motif containing 72 (TRIM72) that expresses in a limited number of tissues including the lung. Nevertheless, the role of alveolar epithelial cell (AEC) repair in the pathogenesis of IPF has not been examined yet.

Method

In this study, we tested the specific roles of TRIM72 in the repair of ATII cells and the development of lung fibrosis. The role of membrane repair was accessed by saponin assay on isolated primary ATII cells and rat ATII cell line. The anti-fibrotic potential of TRIM72 was tested with bleomycin-treated transgenic mice.

Results

We showed that TRIM72 was upregulated following various injuries and in human IPF lungs. However, TRIM72 expression in ATII cells of the IPF lungs had aberrant subcellular localization. In vitro studies showed that TRIM72 repairs membrane injury of immortalized and primary ATIIs, leading to inhibition of stress-induced p53 activation and reduction in cell apoptosis. In vivo studies demonstrated that TRIM72 protects the integrity of the alveolar epithelial layer and reduces lung fibrosis.

Conclusion

Our results suggest that TRIM72 protects injured lungs and ameliorates fibrosis through promoting post-injury repair of AECs.
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Metadata
Title
TRIM72 promotes alveolar epithelial cell membrane repair and ameliorates lung fibrosis
Authors
Xiaofei Cong
Nagaraja Nagre
Jeremy Herrera
Andrew C. Pearson
Ian Pepper
Robell Morehouse
Hong-Long Ji
Dianhua Jiang
Rolf D. Hubmayr
Xiaoli Zhao
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2020
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/s12931-020-01384-2

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